1. Field of the Invention
The present invention relates to an indole derivative which is highly useful for therapy and prophylaxis of hyperlipidemia and arteriosclerosis. The present invention also relates to a method of production of the indole derivative and a lipid lowering agent containing the indole derivative as an active ingredient.
2. Description of the Related Art
Hyperlipidemia which gives an abnormally high level of serum lipid has been considered to be a clinical disease by itself and to be a cause of arteriosclerosis. For amelioration of abnormalities in lipid metabolism, medicines, such as, nicotinic acid or derivatives thereof, clofibrate, and phenyl alkyl ethers having a partial structure of the clofibrate are frequently used. In recent years, melinamide: a linoleamide derivative, probucol: a bisphenol derivative, colestyramine: an ion exchange resin and the like have come to be used for clinical therapy. Furthermore, tazasubrate which has a structure analogous to that of the compound of the present invention is known (Merck Patent G.m.b.H.: Japanese Patent Kokai Sho 56-92881, corresponding to European Patent Application EP 30632 and U.S. Pat. No. 4,294,839). For the present purpose, however, a compound having an indole skeleton like the one of the present invention is not known.
A compound having thioacetic acid group at the 2-position of an indole ring is described in J. Heterocycl. Chem., 8, 903 (1971). This compound, however, has a phenyl group at the 3-position in the structure thereof, which is completely different from the one of the present invention. Moreover, nothing is described regarding the pharmacological activity of the compound.
Recently, low density lipoprotein-cholesterol (LDL-Ch) has been indicated as an arteriosclrosis factor, and high density lipoprotein-cholesterol (HDL-Ch) has been indicated as antiarteriosclerosis factor. That is, the amelioration of the arteriosclerotic index (AI) represented by the ratio of an LDL-Ch value to the a HDL-Ch value in serum by lowering the LDL-Ch value and raising the HDL-Ch value is considered to be important, rather than simply lowering the level of the total cholesterols, triglycerides, and the like. Nevertheless, the medicines used for clinical therapy thereof at present are not satisfactory. Thus the medicine is desired which is effective in ameliorating abnormal lipid metabolism and yet is highly safe.